Methane → HCID 131719899, compound

HRID 975935Notes

Reaction equation

HRID 975935 reaction equation
C.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH2:10][N:9]([C:16]1[CH:25]=[C:24]([NH2:26])[C:23]3[C:18](=[CH:19][C:20]([O:29][CH3:30])=[C:21]([O:27][CH3:28])[CH:22]=3)[N:17]=1)[CH2:8][CH2:7]2.[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35]>C(Cl)Cl.CO>[OH2:3].[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH2:10][N:9]([C:16]1[CH:25]=[C:24]([NH2:26])[C:23]3[C:18](=[CH:19][C:20]([O:29][CH3:30])=[C:21]([O:27][CH3:28])[CH:22]=3)[N:17]=1)[CH2:8][CH2:7]2.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH2:10][N:9]([C:16]1[CH:25]=[C:24]([NH2:26])[C:23]3[C:18](=[CH:19][C:20]([O:29][CH3:30])=[C:21]([O:27][CH3:28])[CH:22]=3)[N:17]=1)[CH2:8][CH2:7]2.[OH2:3]

Participants

6

Reactant 3

HCID 297MethaneHCID 164089AbanoquilHCID 444972Fumaric Acid

Product 1

HCID 131719899HCID 131719899, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-[1-(6, 7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethylidineamino]-4,5-dimethoxybenzonitrile (471 mg, 1.19 mmol, 1.00 equiv) in refluxing anhydrous N,N-dimethylacetamide (24 mL) under argon was added ZnCl2 (339 mg, 2.49 mmol, 2.10 equiv) in three portions over 1 h. The solvent was removed by distillation at 70° C. under high vacuum. Ether (40 mL) was added to the residue, which was broken up with a stirring rod, and the mixture was stirred at 0° C. to precipitate the product. The supernatant was discarded, and the precipitate was washed twice more at 0° C. with ether. The solid residue was stirred with 1 M aq. NaOH (25 mL) and CH2C2 (25 mL) for 10 min, and the aqueous phase was extracted with CH2C2 (2×25 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 493 mg of brown oil, which was flash chromatographed on silica gel (MeOH-CH2Cl2 12:88 followed by 2-propylamine-CH2Cl2 5:95) to afford 151 mg (38%) of 2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxyquinolin-4-ylamine as a tan solid: 1H NMR (300 MHz, CDCl3) δ 2.90 (t, J=5.7 Hz, 2 H), 3.81 (t, J=5.7 Hz, 2 H), 3.86 (s, 3 H), 3.88 (s, 3 H), 3.93 (s, 3 H), 3.97 (s, 3 H), 4.64 (s, 2 H), 6.05 (s, 1 H), 6.66 (s, 1 H), 6.75 (s, 1 H), 7.02 (s, 1 H), 7.23 (s, 1 H); CIMS (CH4) 424 (M+C2H5)+, 396 (M+H)+. To a solution of 2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl) -6,7-dimethoxyquinolin-4-ylamine (150 mg) in hot CH2Cl2 (4.5 mL) and MeOH (1.5 mL) was added a solution of fumaric acid (22.8 mg, 0.196 mmol, 0.50 equiv) in hot MeOH (3.0 mL). The resulting mixture was concentrated and the product was recrystallized from MeOH with hot filtration to afford, after filtration, 85 mg of light brown solid: m.p. 239°-240° C. Calcd. for C22H25N3O4 ·0.5C4H4O4 ·0.75 H 2O: C, 61.73; H, 6.15; N, 9.00. Found: C,61.77; H, 6.17; N, 8.91.

Workup

  1. concentrationThe resulting mixture was concentrated
  2. customthe product was recrystallized from MeOH with hot filtration
  3. customto afford
  4. filtrationafter filtration, 85 mg of light brown solid

Sources & evidence

ORD record
ord-7491378e132f4b758495f340055d4909
Source dataset
uspto-grants-1997_03
Patent number
US05610174

Reaction notes

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